PTEN, A Target of Microrna-374b, Contributes to the Radiosensitivity of Canine Oral Melanoma Cells

Canine oral malignant melanoma (CoMM) is often treated by radiation therapy in veterinary medicine. However, not all cases are successfully managed by this treatment. For improved efficacy of radiation therapy, biomarkers predicting the radiosensitivity of melanoma cells need to be explored. Here, we, first, developed the radioresistant CoMM cell line, KMeC/R. We found that the expression level of phosphatase and tensin homolog (PTEN) of KMeC/R cells was significantly downregulated compared with KMeC cells. Overexpression of PTEN successfully restored the radiosensitivity of KMeC/R cells, and silencing of PTEN significantly increased the radioresistance of the CoMM cells tested. Next, we focused on microRNAs (miRNAs) to explore the mechanisms of downregulation of PTEN in KMeC/R cells. miR-374b was upregulated in KMeC/R cells compared with that in KMeC cells and in the irradiated CoMM cells tested. Furthermore, miR-374b directly targeted PTEN based on the luciferase activity assay. Moreover, the extrinsic miR-374b significantly increased the radioresistance of KMeC cells. In addition, the expression level of PTEN was significantly downregulated and that of miR-374b tended to be upregulated in recurrent CoMM tissues after radiation therapy compared with the pre-treatment tissues. Thus, the current study suggested that the miR-374b/PTEN signaling pathway possibly plays an important role in CoMM radiosensitivity.

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Regulation of melanoma cell growth by a miR-21 loaded targeted delivery system based on microparticles and nanoparticles targeting phosphatase and tensin homolog (PTEN)

Materials Express ◽

10.1166/mex.2021.2095 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1766-1773

Author(s):

Lei Jin ◽

Tong Yang

Keyword(s):

Delivery System ◽

Self Assembly ◽

Targeted Delivery ◽

Melanoma Cells ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

Assembly Method ◽

New Strategy ◽

Low Levels ◽

Phosphatase And Tensin Homologue

The modulatory effect of miR-21 on the proliferation of melanoma cells through stimulation of PTEN (Phosphatase and tensin homologue deleted on chromosome 10) expression was investigated in the current study. PTEN, as a tumor suppressor, is expressed in low levels in melanoma tissues and cell lines. Nevertheless, miR-21 can stimulate cancer development and suppress cell apoptosis. Overexpression of PTEN substantially impaired the proliferation of miR-21-treated melanoma cells. In addition, miR-21 and PTEN were observed to exhibit a combinatorial effect, whereas miR-21 could negatively regulate the expression of PTEN. In conclusion, these findings demonstrate that miR-21 affects melanoma development by targeting PTEN, establishing a new strategy for treating malignant melanoma. Furthermore, in this study, microparticles and nanoparticles were employed as carriers to construct, through the self-assembly method, nanocapsules carrying miR-21 in order to develop an efficient nanocapsule delivery system of miR-21 against melanoma cells.

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ZNF139 increases multidrug resistance in gastric cancer cells by inhibiting miR-185

Bioscience Reports ◽

10.1042/bsr20181023 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 7

Author(s):

Bibo Tan ◽

Yong Li ◽

Qun Zhao ◽

Liqiao Fan ◽

Dong Wang

Keyword(s):

Gastric Cancer ◽

Drug Resistance ◽

Multidrug Resistance ◽

Cell Lines ◽

Zinc Finger Protein ◽

Luciferase Activity ◽

Cell Activity ◽

Expression Level ◽

Activity Assay ◽

Luciferase Activity Assay

It has been reported that the expression of zinc finger protein 139 (ZNF139) and microRNA-185 (miR-185) were associated with proliferation, drug resistance of gastric cancer (GC) cells. However, the detailed mechanisms have not been fully investigated. The expression of ZNF139 in both GC tissues and cell lines was tested, then SGC7901/ADR or SGC7901 cells were transfected with ZNF139-siRNA, miR-185 analog, or pcDNA-ZNF139. Cell activity was determined by MTT assay. Real-time PCR and Western blot were utilized to detect ZNF139, miR-185, and multidrug resistance (MDR) related genes including MDR1/P-gp, GST-π, MRP-1, Bcl-2, TS and Bax. ChIP and dual luciferase activity assay were used to investigate regulation between ZNF139 and miR-185. Increased ZNF139 and decreased miR-185 expression were detected in GC tissues and cell lines. Transfection with ZNF139-siRNA into SGC7901/ADR cells markedly increased expression of miR-185, and treating with chemotherapeutic drugs ADR, 5-FU, L-OHP, the survival rate of SGC7901/ADR cells obviously decreased after ZNF139-siRNA transfection. On the other hand, transfection with pcDNA-ZNF139 in GC cell line SGC7901 resulted in an increased expression level of ZNF139 and a decline in the expression level of miR-185, meanwhile drug resistance of GC cells was clearly enhanced to ADR, 5-FU, L-OHP. Dual luciferase activity assay demonstrated that ZNF139 inhibited transcriptional activities of miR-185’s promoter in cells transfected with the reporter plasmid encompassing the upstream promoter region of miR-185 along with pcDNA-ZNF139. Our data reveal that ZNF139 might promote MDR gene MDR1/P-gp, MRP-1 and Bcl-2 by prohibiting miR-185.

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Analysis of the expression level and methylation of tumor protein p53, phosphatase and tensin homolog and mutS homolog 2 in N-methyl-N-nitrosourea-induced thymic lymphoma in C57BL/6 mice

Oncology Letters ◽

10.3892/ol.2017.6721 ◽

2017 ◽

Vol 14 (4) ◽

pp. 4339-4348 ◽

Cited By ~ 1

Author(s):

Xueyun Huo ◽

Zhenkun Li ◽

Shuangyue Zhang ◽

Changlong Li ◽

Meng Guo ◽

...

Keyword(s):

Expression Level ◽

Phosphatase And Tensin Homolog ◽

Thymic Lymphoma ◽

Tensin Homolog ◽

Protein P53 ◽

Tumor Protein P53

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Chamazulene-Rich Artemisia arborescens Essential Oils Affect the Cell Growth of Human Melanoma Cells

Plants ◽

10.3390/plants9081000 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1000

Author(s):

Alessandra Russo ◽

Maurizio Bruno ◽

Rosanna Avola ◽

Venera Cardile ◽

Daniela Rigano

Keyword(s):

Essential Oils ◽

Defense Mechanisms ◽

Membrane Integrity ◽

Melanoma Cells ◽

Human Malignant Melanoma ◽

Phosphatase And Tensin Homolog ◽

Cell Membrane Integrity ◽

Melanoma Cancer ◽

Tensin Homolog ◽

Ic50 Values

Artemisia arborescens is an aromatic shrub whose essential oils are considered a potential source of molecules with industrial and pharmaceutical interest. The chemical profile of A. arborescens essential oils (EOs) was shown to be quite variable and various chemotypes have been identified. In this study, we compared the EOs composition of A. arborescens leaves and flowers collected from four different locations in Sicily. The EOs were assayed for their antiproliferative activity against A375 human malignant melanoma cells, also testing cell viability and cell membrane integrity. The evaluation of DNA fragmentation and caspase-3 activity assay was employed for the detection of apoptosis. The expression of Bcl-2, Bax, cleaved caspase-9, PTEN (Phosphatase and tensin homolog), Hsp70 (Heat Shock Protein 70 kilodaltons) and SOD (superoxide dismutase) proteins was evaluated by Western blot analysis. The levels of ROS and GSH were also analyzed. Results show that EOs presented significant differences in their composition, yield, and cytotoxic activity depending on the collection site. The chamazulene/camphor-rich EOs from plants collected in Acqua Calda (Lipari) resulted particularly active on melanoma cancer cells (IC50 values of 6.7 and 4.5 µg/mL), being able to trigger apoptotic death probably interfering with endogenous defense mechanisms. These oils may be considered as a natural resource of chamazulene, containing this compound up to 63%.

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Low expression level of phosphatase and tensin homolog deleted on chromosome ten predicts poor prognosis in chronic lymphocytic leukemia

Leukemia & Lymphoma ◽

10.3109/10428194.2012.733880 ◽

2012 ◽

Vol 54 (6) ◽

pp. 1159-1164 ◽

Cited By ~ 10

Author(s):

Zhi-Jian Zou ◽

Run Zhang ◽

Lei Fan ◽

Li Wang ◽

Cheng Fang ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Poor Prognosis ◽

Lymphocytic Leukemia ◽

Expression Level ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog ◽

Low Expression

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Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy

Oncotarget ◽

10.18632/oncotarget.1926 ◽

2014 ◽

Vol 5 (10) ◽

pp. 3273-3286 ◽

Cited By ~ 27

Author(s):

Rachel Abbotts ◽

Rosalyn Jewell ◽

Jérémie Nsengimana ◽

David J Maloney ◽

Anton Simeonov ◽

...

Keyword(s):

Melanoma Cells ◽

Personalized Therapy ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

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High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog)

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314458 ◽

2020 ◽

Vol 40 (8) ◽

pp. 1854-1869

Author(s):

Keith A. Strand ◽

Sizhao Lu ◽

Marie F. Mutryn ◽

Linfeng Li ◽

Qiong Zhou ◽

...

Keyword(s):

Protein Expression ◽

High Throughput ◽

Knockout Mice ◽

Vascular Remodeling ◽

Dna Methyltransferase ◽

Dna Methyltransferase 1 ◽

Protective Effects ◽

High Throughput Screen ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

Objective: Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Conclusions: Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.

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LINC01089 functions as a ceRNA for miR-152-3p to inhibit non‐small lung cancer progression through regulating PTEN

Cancer Cell International ◽

10.1186/s12935-021-01846-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Huixian Zhang ◽

Hao Zhang ◽

Xingya Li ◽

Siyuan Huang ◽

Qianqian Guo ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Expression Level ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Loss Of Function ◽

Protein Coding ◽

Tensin Homolog ◽

Pten Mrna

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. Methods The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3’UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. Results LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. Conclusions Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis.

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